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1998 Fiscal Year Final Research Report Summary

脂肪細胞における肥満遺伝子とインスリン作用関連遺伝子の制御機構の研究

Research Project

Project/Area Number 09671053
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

NISHIMURA Haruo  Kyoto Univsity, Clinical Science and Medicine, Assistant Prof., 医学研究科, 助手 (40281729)

Co-Investigator(Kenkyū-buntansha) HOSODA Kiminori  Kyoto Univsity, Environmetal Study, Assistant Prof., 人間環境学研究科, 助手 (40271598)
YOSHIMASA Yasunao  Kyoto Univsity, Clinical Science and Medicine, Lecturer, 医学研究科, 講師 (00252437)
Project Period (FY) 1997 – 1998
KeywordsLeptin / Thiazolidinedione / Insulin Action / Adipocyte / Skeletal Muscle / Obesity
Research Abstract

(1) Effect of thiazolidinediones on leptin production and insulin action in rat adipocytes. Thiazolidinedione, an insulin sensitizer, reduced protein and mRNA levels of leptin in rat adipocytes after 24 hours. This compound also increased 2-deoxyglucose uptake in the adipocytes. However, mRNA level of leptin and insulin action were not changed, when the adipocytes were incubated with exogenous leptin for 24 hours, Thus it is suggested that exogenous leptin dose not affect the primary culture of adipocytes directly.
(2) Effect of leptin on insulin action in culture of skeletal muscle Leptin did not affect the insulin action including insulinsignaling systems and glucose uptake in culture of skeletal muscles (L6 cells).
(3) Insulin action in leptin transgenic mouse Leptin transgenic mouse showed no accumulation of adipocytes, both white and brown adipocytes. In vivo insulin action determined by intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT) showed enhanced insulin sensitivity in the transgenic mice. It is suggested that leptin has lipoatrophic effect on adipocytes and insulin action, and that insulin action is enhanced Through central nervous systems by leptin.
(4) Concentration of plasma leptin in human There were correlations between plasma leptin and % fat , body mass index significantly. And the was also gender difference in leptin concentration (male<female). However aging did not affect the concentration. We also found some polymorphisms in leptin gene, but there were no relation between leptin and the polymorphisms in Japanese obese subjects.

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Azuma N, Yoshimasa Y, Nishimura H, et al.: "The significance of the Trp64Arg mutation of the B3-adrenergic receptor gene in impaired glucose tolerance, non-insulin -dependent diabetes mellitus and insulin resistance in Japanese subjects." Metabollsm. 47. 456-460 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yonemitsu Y, Shintani M, Nishimura H, et al.: "Effect of Leptin and Troglitazone on Glucose Uptake in L6 Myotcytes." Diabetes. 47. 272A (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shintani M, Nishimura H,Yonemits S, et al.: "Differential Regulation of Free Fatty Acid and Troglitazone on Leptin and GLUT4 in Rat Adipocytes." Diabetes. 47. 319A (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuda J, Hosoda K, Nishimura H, et al.: "Increased adipose expression of uncoupling protein-3 gene by thizolidinediones in Wister fatty rats and in cultured adipocytes." Diabetes. 47. 1809-1814 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masuzaki H, Nishimura H, Yoshimasa Y, et al.: "Nonadipose tissue production of leptin : leptin as a novel placenta-derived hormone in humans." Nature Medicine. 3. 1029-1033 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuoka N, Nishimura H, Yoshimasa Y, et al.: "Human leptin receptor gene in obese Japanese subjects : evidence against either obesity-causing mutations or association of sequence variants with obesity." Diabetologia. 40. 1204-1210 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimura H,Shintani M,Yamamoto Y,Suga J,Tanaka T,Takaya K,Yoshimasa Y,Nakao K.: "Leptin Decreases Protein and mRNA Levels of GLUT4 in Rat Adipocytes." Diabetes. 46. 59A (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shintani M,Nishimura H,Yamamoto Y,Suga J,Tanaka T,Hanaoka I,Yoshimasa Y,Nishi S,Nakao K.: "Differential Regulation of Isoproterenol and Troglitazone on Leptin and GLUT4 in Rat Adipocytes." Diabetes. 46. 86A (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Azuma N,Nishimura H,Yamamoto Y,Suga J,Shigemoto M,Nishi S,Yoshimasa Y.: "Significance of the Trp64Arg Mutation of 3-Adrenergic Receptor Gene in Insulin Resistance." Diabetes. 46. 168A (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masuzaki H,Ogawa Y,Hosoda K,Miyawaki T,Hanaoka I,Hiraoka J,Yasuno A,Nishimura H,Yoshimasa Y,Nishi S,Nakao K.: "Glucocorticoid regulation of leptin synthesis and secretion in humans : elevated plasma leptin levels in Cushing's syndrome." J Clin Endocrinol Metab. 82. 2542-2547 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masuzaki H,Ogawa Y,Sagawa N,Hosoda K,Matsumoto T,Mise H,Nishimura H,Yoshimasa Y,Tanaka I,Mori T,Nakao K.: "Nonadipose tissue production of leptin : leptin as a novel placenta-derived hormone in humans." Nat Med. 3. 1029-1033 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuoka N,Ogawa Y,Hosoda K,Matsuda J,Masuzaki H,Miyawaki T,Azuma N,Natsui K,Nishimura H,Yoshimasa Y,Nishi S,Thompson DB,Nakao K.: "Human leptin receptor gene in obese Japanese subjects : evidence against either obesity-causing mutations or association of sequence variants with obesity." Diabetologia. 40. 1204-1210 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shigemoto M,Nishi S,Ogawa Y,Isse N,Matsuoka N,Tanaka T,Azuma N,Masuzaki H,Nishimura H,Yoshimasa Y,Hosoda K,Nakao K.: "Molecular screening of both th epromoter and the protein coding regions in the human ob gene in Japanese obese subjects with non-insulin-dependent diabetes mellitus (NIDDM)." Eur J Endocrinol. 137. 511-513 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuda J,Hosoda K,Itoh H,Son C,Doi K,Tanaka T,Fukunaga Y,Inoue G,Nishimura H,Yoshimasa Y,Yamori Y,Nakao K.: "Cloning of rat uncoupling protein-3 and uncoupling protein-2 cDNAs : their gene expression in rats fed high-fat diet." FEBS Lett. 418. 200-204 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Azuma N,Yoshimasa Y,Nishimura H,Yamamoto Y,Masuzaki H,Suga J,Shigemoto M,Matsuoka N,Tanaka T,Sattoh N,Igaki T,Miyamoto Y,Itoh H,Yoshimasa T,Hosoda K,Nishi S,Nakao K.: "The significance of the Trp64Arg mutation of the B3-adrenergic receptor gene in impaired glucose tolerance, non-insulin-dependent diabetes mellitus and insulin resistance in Japanese subjects." Metabolism. 47. 456-460 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yonemitsu Y,Shintani M,Yamamoto Y,Matsuoka N,Suga J,Hosoda K,Yoshimasa Y,Nishimura H.: "Effect of Leptin and Troglitazone on Glucose Uptake in L6 Myotcytes." Diabetes. 47. A272 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shintani M,Nishimura H,Yonemits S,Hosoda K,Hiraoka J,Matsuoka N,Yoshimasa Y,Nishi S,Nakao K.: "Differential Regulation of Free Fatty Acid and Troglitazone on Leptin and GLUT4 in Rat Adipocytes." Diabetes. 47. 319A (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuda J,Hosoda K,Itoh H,Son C,Doi K,Hanaoka I,Inoue G,Nishimura H,Yoshimasa Y,Yamori Y,Odaka H,Nakao K.: "Increased adipose expression of uncoupling protein-3 gene by thizolidinediones in Wister fatty rats and in cultured adipocytes." Diabetes. 47. 1809-1814 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, T,Hosoda K,Itoh H,Son C,Doi K,Hanaoka I,Inoue G,Nishimura H,Yoshimasa Y,Yamori Y,Odaka H,Nakao K.: Diabetologia. (in press.). (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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